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Solvation in octanol: Parametrization of the continuum MST model

Posted September 5th, 2013 by ccurutchet
TitleSolvation in octanol: Parametrization of the continuum MST model
Publication TypeJournal Article
Year of Publication2001
AuthorsCurutchet, C, Orozco M, Luque FJ
JournalJournal of Computational Chemistry
Volume22
Issue11
Pagination1180 - 1193
Date Published2001
ISBN Number0192-8651
Keywordsaqueous-solutions, continuum MST model, electrostatic interaction, free-energy perturbation, iv atomic charges, neutral molecules, nucleic-acid bases, octanol, organic-compounds, partition-coefficients, tetrazole isomerism, water-octanol
AbstractThis study reports the parametrization of the HF/6-31G(d) version of the MST continuum model for n-octanol. Following our previous studies related to the MST parametrization for water, chloroform, and carbon tetrachloride, a detailed exploration of the definition of the solute/solvent interface has been performed. To this end, we have exploited the results obtained from free energy calculations coupled to Monte Carlo simulations, and those derived from the QM/MM analysis of solvent-induced dipoles for selected solutes. The atomic hardness parameters have been determined by fitting to the experimental free energies of solvation in octanol. The final MST model is able to reproduce the experimental free energy of solvation for 62 compounds and the octanol/water partition coefficient (log P(ow)) for 75 compounds with a root-mean-square deviation of 0.6 kcal/mol and 0.4 tin units of log P), respectively. The model has been further verified by calculating the octanol/water partition coefficient for a set of 27 drugs, which were not considered in the parametrization set. A good agreement is found between predicted and experimental values of log P(o/w), as noted in a root-mean-square deviation of 0.75 units of log P. (C) 2001 John Wiley & Sons, Inc.